Genomic analysis of Bartonella identifies type IV secretion systems as host adaptability factors

Abstract

The bacterial genus Bartonella comprises 21 pathogens causing characteristic intraerythrocytic infections. Bartonella bacilliformis is a severe pathogen representing an ancestral lineage, whereas the other species are benign pathogens that evolved by radial speciation. Here, we have used comparative and functional genomics to infer pathogenicity genes specific to the radiating lineage, and we suggest that these genes may have facilitated adaptation to the host environment. We determined the complete genome sequence of Bartonella tribocorum by shotgun sequencing and functionally identified 97 pathogenicity genes by signature-tagged mutagenesis. Eighty-one pathogenicity genes belong to the core genome (1,097 genes) of the radiating lineage inferred from genome comparison of B. tribocorum, Bartonella henselae and Bartonella quintana. Sixty-six pathogenicity genes are present in B. bacilliformis, and one has been lost by deletion. The 14 pathogenicity genes specific for the radiating lineage encode two laterally acquired type IV secretion systems, suggesting that these systems have a role in host adaptability.

Strategies of exploitation of mammalian reservoirs by Bartonella species

“…The use of these tools in conjunction with judicious screening in relevant animal models (rats and mice respectively) has resulted in the identification of numerous genetic sequences, the integrity of which are necessary for the establishment of bacteraemia by bartonellae [4,19]. Those genetic sequences can be classified into six groups: (1) genes previously implicated in Bartonella infection of its mammalian hosts, (2) genes encoding cell envelope components, (3) genes encoding proteins involved in metabolism, (4) phage-related genes, (5) genes encoding proteins of unknown function and (6) intergenic regions.…”

“…The putative promoter region of the operon was also identified and its expression was shown to be induced when B. henselae was cultivated with human microvascular endothelial cells [46]. The operon was subsequently identified in other Bartonella species, and its necessity for host interaction was demonstrated using a B. tribocorum -rat and subsequently a B. birtlesii -mouse infection model [4,19,47]. Experimentation using these models revealed that although the VirB/D4 system was essential for exploitation of the primary niche, it was dispensable for the subsequent erythrocytic infection [48].…”

“…A homolog of the VirB/D4 system, Vbh, has also been identified and all Bartonella species except B. bacilliformis possess at least one of these two T4SSs [4]. Comparative genomics have indicated that these systems were acquired by a common ancestor of lineage 2 and 3 Bartonella species following its divergence from lineage 1 that carries B. bacilliformis (Figure 1) [5].…”

“…The remaining “modern” species form two further lineages, with lineage 2 containing the four ruminant-associated species ( Bartonella bovis, Bartonella capreoli, Bartonella chomelii and Bartonella schoenbuchensis ), and lineage 3 containing the remaining 19 species (Figure 1). Within lineage 3, Bartonella clarridgeiae is the outlier, and phylogenetic studies that have also included as yet only partially characterised bartonellae have suggested that this species is a representative of a fourth lineage within the genus [4,5]. The complete genome sequences of six Bartonella species ( B. bacilliformis, B.clarridgeiae, Bartonella grahamii, Bartonella henselae, Bartonella quintana and Bartonella tribocorum ) have been published to date, although efforts to sequence the genomes of all remaining species and numerous partially-characterised bartonellae are also underway.…”

“…The complete genome sequences of six Bartonella species ( B. bacilliformis, B.clarridgeiae, Bartonella grahamii, Bartonella henselae, Bartonella quintana and Bartonella tribocorum ) have been published to date, although efforts to sequence the genomes of all remaining species and numerous partially-characterised bartonellae are also underway. The sizes of the published genomes range from 1.45 Mb to 2.62 Mb [4,6]. …”